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Патент USA US3047594

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United States Patent Office
3,647,579
?atenterii July 3i, 19(82
ti,
efficiently effects the oxidation of the N-oxides of all of
3, 47,579
PRGQW‘ '
the tertiary amines which are known to oxidize to the
corresponding N-oxides, and in fact my new process is
PREEJARPIG N-OXEBIES
Robert ‘S. Witman, ‘Wsst‘iield, NJ, assignor to Sheil Gil
applicable generally to the oxidation of all tertiary amines
(Iornpany, a corporation of Delaware
No Drawing.
i i
Filed
.liuly 18, 1958, §er. No. ‘749,345
to the corresponding N-oxides.
Since my new process
employs only stable, easily handled materials, relatively
inexpensive, re-usable catalysts, and gives much higher
This invention pertains to a process for the preparation
of N-oxides—that is, amine oxides.
reaction rates than have heretofore been possible, it lends
itself admirably as a general method for the large-scale
More particularly,
this invention provides a novel, improved process for the
preparation of N-oxides. The new process also effects
preparation of N-oxides of tertiary organic bases-Le, 10 much more efficient use of hydrogen peroxide.
tertiary amines.
Any tertiary amine in which the amino nitrogen atom
The N-oxides are a class of compounds of which vari
ous members have been found to have properties which
make them useful for a Wide variety of purposes. Thus,
is the primary reactive moiety is oxidized to the corre
sponding N-oxide by my new process. Suitable amines
thus include the tertiary amines in which the groups di
the halo-pyridine N-oxides have been found to be effec
rectly bonded to the amino nitrogen atom are hydro
tive fungicides, as have the N-oxides of the nitrogenous
carbon groups, and those in which the groups directly
condensation products of methylol-forming phenolic com
bonded to the amino nitrogen atom are substituted-hydro
pounds, formaldehyde and aliphatic secondary amines.
carbon in character. The groups bonded to the amino
These latter N-oxides also have been found to be of value 20 nitrogen atom may be aliphatic or ‘aromatic in character.
as moth-proo?ng agents, and as bactericides, as ?nishing
The aliphatic groups may be of branched-chain or of
agents for textiles, as water-proo?ng agents for textiles,
and for rendering textiles more receptive to dyes. Also,
the N-oxides of heterocyclic bases, such as the phenan
straight—chain con?guration, or they may be cyclic in
character; they may be saturated, or they may be ole?ni
throlines, quinoxalines, quinolines, isoquinolines and py
ridines, have been found to have valuable therapeutic
properties and low mammalian toxicity. N-oxides also
groups preferably are excluded, since the acetylenic link
tivity of the amino nitrogen atom. The amino nitrogen
have been found to be useful as stabilizers for unsatu
atom may form a part of a heterocyclic ring, and in such
cally unsaturated. Actylenically unsaturated aliphatic
age in some cases may interfere with the necessary reac
rated compounds such as styrene, and as wetting agents,
Washing agents, cleaning agents, emulsifying agents, and
for other uses which involve modi?cation of the surface
properties of aqueous media. Many of the N -oxides also
cases, the remaining atoms of the ring may be only carbon
03 C; atoms, or they may be such atoms as the oxygen atom,
the sulfur atom, metal atoms or semi-metal atoms. The
suitable tertiary amines may be homogeneous in char
acter-—all of the groups bonded to the amino nitrogen
ring being similar in character—or they may be hetero,
are of interest as raw materials for the preparation of
other valuable compounds.
It has been proposed that the N-oxides be prepared
by reacting a tertiary amine with perbenzoic acid, peroxy
geneous in character—i.e., mixed amines wherein two or
more of the groups bonded to the amino nitrogen atom
acetic acid or like organic per-acids, in an organic solvent.
However, such organic per-acids are highly unstable, so I
are dissimilar in character.
Suitable amines thus include those wherein the groups
bonded to the amino nitrogen atom are alkyl, aryl,
that they must be prepared freshly just before use, and
great caution must be exercised in their use to prevent 40
their detonation.
Further, these organic per-acids are
expensive to prepare and use. Consequently, processes
involving the use of such acids are not feasible for the
large-scale preparation of ‘til-oxides.
Examples of the suitable types of tertiary amines in
clude the trialkyl amines such as trimethyl, tributyl, tri
It also has been proposed that the N-oxides be pre
pared by reacting a tertiary amine with hydrogen perox~
ide in an aqueous reaction medium.
octyl, methyl diethyl, isopropyl diamyl, pentyl' methyl
This method like
butyl and like amines, alkyloi amines such as triethanola
wise is not feasible for the large-scale production of N
mine, triisopropanolamine, and the like, mixed alkyl
alkyloi amines, such as diethyl ethanolamine, aryl
oxides because the reaction times involved are much too
long.
To overcome the shortcomings of such processes, it
has been proposed that the reaction of a tertiary amine
with hydrogen peroxide be carried out in the presence of
particular reaction media, particularly oxygen-containing
organic liquids such as lower carboxylic acids (glacial
acetic acid in particular) and lower ketones (acetone in
particular) .
These latter proposals have not provided any satisfac
tory method for preparing N-oxides, inasmuch as the
elfectiveness of the use of particular solvents in e?ecting
the oxidation of the amine to the N-oxide varies greatly
from case to case.
Thus, in some cases, the use of an
oxygen-containing organic solvent results in e?icient oxi
dation of the amine, while in other cases such a solvent
is Wholly ineffective in promoting the oxidation of the
amine.
I have now discovered that tertiary amines, as a class,
are easily and e?‘iciently oxidized to the corresponding
N-oxides by reacting those amines with hydrogen perox
aralkyl, alkaryl, alkenyl, alkenyl-aryl, aralkenyl groups
i.e., hydrocarbon groups—or alkylol, haloalkyl, haloaryl,
hydroxyaryl, haloalkaryl, haloaralkyl, haloalkenyl or ‘like
substituted-hydrocarbon groups.
50
amines such as triohenylamine, mixed alkyl ‘aryl
amines such as dimethyl aniline, araikyl amines such
as tribenzylamine, alkaryl amines such as tri-p-tolyl
amine, mixed, allyl diethylamine, phenyl ethyl allylamine
and the like, halogen~substituted hydrocarbon amines
such as tris(beta-chloroethyl)amine, beta-chloroethyl di
methylamine, tribromomethyl diethylamine, phenyl beta,
'beta-dichloroethylamine, tris(p-chlorophenyl)amine, p
bromophenyl dihexylamine, ‘and the homologs and ana
logs of such amines. Suitable amines of interest because
of the properties of the corresponding N-oxides are the
trialkylamines containing up to 35 carbon atoms, and
particularly such amines wherein one of the alkyl groups
is a long-chain alkyl group of from 8 to 20 carbon atoms
(such as the capryl, lauryl, cetyl, stearyl or octadecenyl
groups) and the other two alkyl groups are lower alkyl
groups of up to 6 carbon atoms each, or those other two
alkyl groups form a single alkylene group, as in the
piperidine or pyrrolidine rings.
Suitable amines also of
interest ‘because of their amine oxides are the tertiary
ide in the presence of unstable inorganic per-compounds
70 amines of the formula (R) (R') (R”)N, wherein R is a
of acid—forming elements of groups VA, VIA, VIE and
hydroaromatic moiety, or wherein R is an alkyl group
VIII of the periodic table, as catalyst. My new process
of up to 20 carbon atoms bonded to the nitrogen atom
3,047,579
3
by an oxyalkylene (—-O-alkylene-) group, by an amido
alkylindolcs, N-alkyl pseudoindoles, N-alkyl isoindoles
and pseudoisoindoles, 4-quinolizine, the N-alkyl 2~benz
alkylene (—-C(O)NH-alkylene-) group, or by an aro
azocines, the N-alkyl 7,8~benzoheptamethylenimines, the
matic nucleus such as the phenyl nucleus. Still another
N-alkyl cyclopenta(b) -pyrroles, and the corresponding
group of N~oxides of interest are those derived from
U! (c)-pyrrol_es, the N-alkyl nortropanes, the N-alkyl 1,4
amines of the structurev
and 1,6-pyrro1opyridines and S-pyrindoles, the N-alkyl
aliphatic
oxazolo(5.4-b)pyridines, the various isomeric diazacyclo
long-chain cycloalkyls, such as 1,15-diazacyclotriacon
tane, the various isomeric tetrazocyclo-long-chain cyclo
aliphatic
wherein R is an aromatic or substituted-aromatic nucleus, 10 alkyls, such as 1,4,8,ll-tetrazotetradecane, the N-alkyl-l
azapiro(2.4)heptanes, (2.5)octanes and the like, conidine,
this class of compounds being condensation products of
and other similar tertiary heterocyclic amines.
According to the process of this invention, the tertiary
amine is oxidized to the corresponding N-oxide by react
Patents Nos. ‘2,031,557, 2,033,092, 2,036,916, 2,045,517
ing the amine with hydrogen peroxide in the presence of a
and 2,220,835. The precise nature of such amines and 15 catalyst consisting of an unstable inorganic per-compound
detailed descriptions thereof is set out in the last-men
of an acid-forming element of groups VA, VIA, VIB and
tioned of this series of patents.
VIII of the periodic table. These catalysts are provided
A particularly wide variety of properties are exhibited
by the oxides and/or acids of the speci?ed elements and
by the N-oxides of heterocyclic bases wherein the amino
nitrogen atom is one member of the heterocyclic ring, 20 acid salts of those acids, which oxides, acids or acid salts
form inorganic peracids or acid salts of inorganic per
any valence bond of the trivalent nitrogen atom not in
acids (persalts) in the reaction zone. Although the actual
volved in the ring being satis?ed by a hydrocarbon group,
catalysts are the per-compounds of the acid-forming ele
or a halo- or hydroxy-substituted hydrocarbon group as
methylol-forming phenolic compounds, formaldehyde and
aliphatic secondary amines described in United States
set out hereinbefore. Preferably, the amines from which
ments of groups VA, VI and VIII, these catalysts are
35 carbon atoms, the heterocyclic moiety containing not
oxides, acids or acid salts of those elements. Herein,
for brevity, the source oxides, acids or acid salts also will
such N-oxides are prepared contain not more than about 25 actually formed in situ in the reaction zone from the
more than about 20 carbon atoms. Heterocyclic amines
be termed “catalysts.” Any of the oxides, acids and acid
salts of the acid-forming elements of groups VA, VI and
VIII of the periodic table which are known to be effective
wherein the heterocyclic ring involves only nitrogen,
carbon, oxygen and sulfur atoms, and any substituent
group or groups is(are) hydrocarbon, preferably lower
in promoting hydroxylation of ethylenic compounds by
alkyl or phenyl, halogen or hydroxyl are preferred.
hydrogen peroxide are suitable as catalysts in the present
These amines suitably may contain but one, or they may
Thus, acids, salts of acids, or oxides which re
. PI‘OCCSS.
contain two or more amino nitrogen atoms, and may con
act readily with hydrogen peroxide to form peracids can
tain one, or they may contain two or more hetero rings,
one or more than one amine nitrogen atom being present 35 be used. Oxides and acids of the acid-forming elements
in each ring.
Typical of such heterocyclic N-oxides are those derived
from such heterocyclic amines as pyridine and the various
of group VI of the periodic tableare a particularly useful
class of catalysts. These oxides may be used as such,
substituted pyridines, such as the alkyl-substituted pyri
dines, including both the N~substituted hydropyridines
(dihydro-, tetrohydro- and hexahydropyridines), and the
C-substituted pyridines such as the picolines, lutidines,
collidines and parvolines, phenylpyridine, pyridyl-pyri
dines, halo-substituted pyridines, such as chloropyridine,
dibromopyridine, ‘and the like, quinoline and its substitu
tion products, isoquinoline, hydroxyquinoline, and the
various hydroquinolines and their substitution products,
phenanthrolines and their substitution products, the quin
oxalines, and other pyrazines, such as pyrimidine, pyra
may be convertedto the salts, preferably acid salts, or
40 partial salts, thereof particularly the alkali metal or am
monium salts thereof. Alkaline earth metal and other
salts of these acids likewise may be used, though they are
as may the acids themselves be used, or the acids or oxides
somewhat less eifective in some cases.
aration are set out in detail in United States Patents Nos.
2,754,325 and 2,773,909. For the purpose of brevity
without sacri?ce of detail, the portions of U.S. 2,754,325
and U.S. 2,773,909 describing the heteropoly acids of-the
acid forming elements of group VI of the periodic table
zine and the like. Speci?c examples of other suitable ter
tiary amines in the preparation of N-oxides by the proc
ess of this invention include 2-azirine, N-substituted 2
aziridines, 1,3-diazete, uretine, N-alkyl uretines, l-alkyl-,
3-alkyl-, and 1,3-dialkyl-1,2-diazetidines, N- and N,N'
substituted piperazines, azete, N-alkyl azetines, N-alkyl
acetidines, oxazole, N-alkyl oxazolines, N-alkyl oxa'zoli
dines, l-alkyl-imidazoles, 1-alkyl-, 3.-alkyl- and 1,3-dialkyl
dines, l-alkyl-imidazoles, l-alkyl-, 3-alkyl- and 1,3-dialkyl
imidazolines, the corresponding alkyl-substituted imidazo
lidines, N~alkyl azepines, N-alkyl azocycloheptanes, iso
azepine and A'-hexamethyleneimine, l-alkyl-, 5-alkyl- and
1,S-dialkyl-1,5-diazacyclooctanes, 1-alkyl-1,4-diazonines,
N-alkyl azacyclooctaues, azocine, N-alkyl azocyclono
nanes, 1-alkyl-, 4-alkyl- and 1,4-dialkyl-1,4-diazocyclodec
anes, the various N-alkyl substituted 1,3-, 1,4- and 1,6
diazacyclohendecanes, and the various N-alkyl-substituted
1,2-, 1,4-, and 1,7-diazacyclododecanes, 2- and 4-isomida
zoles, the various N-alkyl-substitution products thereof,
the various N-alkyl pyrroles, pyrrolines and pyrrolidines,
2-pyrrolenine, 3-pyrrolenine, 1,3,5-dioxazine, l,'3,5,2-oxa
diazine, 1,3,5,2-thiadiazine, 1,3,2-oxazine, l,3,4-'oxazine
Also, there may
be used the heteropoly forms of the acids of the acid
45 forming elements of group VI of the periodic table;
Heteropoly acids of this kind which are suitable as catalysts
in the process of this invention and methods for their prep
are hereby incorporated into and made a part of the dis
closures of this speci?cation. Of all of these catalysts, the
55 oxides, acids and acid salts of tungsten have proven to be
the most useful due to their selectivity--i.e., their ability
to promote the desired oxidation of the amine to the N
‘oxide with a minimum of undesirable side reactions—and
to their high level of activity. Preferred catalysts therefore
60 are those which are based on tungsten, including tungstic
oxide, tungstic acid, and the polytungstic acids, including
both the homopolytungstic acids and the heteropolytung
stic acids, and the salts of such acids, particularly the acid
salts, including tungstic acid and the acid tungstates, boro
65 tungstic acid and borotungstates, chromotungstic acid and
chromotungstates, phosphotungstic acid and phospho
tungstates, selenotungstic acid and selenotungstates, and
the like.
.
As a general rule, an amount of the catalyst between
70 about 1.0% and about 20%, based on the number of moles
of amine reactant charged, will effectively catalyze the re
and their thia analogs, pentoxazoline and N-alkyl pent
oxazolidines, the N-alkyl ,homomorpholines, the various
isomeric oxadiazepines, triazepines, oxazepines and their
thia analogs, and the N-alkyl substitution products, N 75
action between the amine and the hydrogen peroxide.
In many cases, even less of the catalyst-—e.g., as little as
0.1% of the amine on a molar basis-will be suf?cient,
whilelin most cases it will be ‘found that ‘little additional
5
3,047,579
6
advantage over the use of lesser amounts of the catalyst
are realized by using an amount of catalyst in excess of
the case of the aliphatic tertiary amines. Suitable acids
about 30% of the number of moles of amine charged.
The hydrogen peroxide employed may be in the form of
these, acetic acid and propionic acid are the most useful,
an anhydrous gas, or liquid or it may be in the form of an
aqueous solution containing from about 10% to about
90% by Weight of hydrogen peroxide. Particularly useful
are the commercially available aqueous solutions con
taining from about 35% to about 70% by weight of hy
drogen peroxide. it is preferable that the highest prac
tical concentration of hydrogen peroxide consistent with
safe handlin? be employed because the presence or" higher
concentrations of hydrogen peroxide in the reaction mix
ture depresses the formation of side products and results
in the formation of higher yields of the desired N-oxide
product. For the same reason, ‘while it is quite feasible
to employ stoichiometric quantities of the hydrogen per
oxide relative to the amine reactant—-i.e., one mole of
hydrogen peroxide per mole of amine~it is desirable that
the hydrogen peroxide be present in the reaction Zone 20
in an amount somewhat in excess of the theoretical
amount. The excess of hydrogen peroxide need not ex
ceed about 100%, and in most cases an excess of hydrogen
peroxide of about 50% will be found sufficient for the
desired purpose. At least a 10% excess of hydrogen per
oxide should be provided.
The oxidation of the amine can be carried out at at
mospheric, superatrnospheric or subatmospheric pressure,
as may be desirable.
In the great majority of cases, it
will be found that operation at substantially atmospheric
pressure will be found to be most convenient. Preferred
temperatures for effecting the reaction are of the order
of from about 40° C. to about 80° C, temperatures of
from about 50 to 60° (3., being generally most useful.
A temperature of at least about 25° C. will generally be
found necessary to obtain practical reaction rates. In
most cases, little advantage will be obtained through the
use of temperatures in excess of about 100° C, as com
pared to the use of somewhat lower temperatures. Under
these conditions of temperature and pressure, reaction
times of the order of from about one-half hour to about
ten hours will be found suilicient to e?ect the desired
reaction to completion.
in many cases, the reaction of the amine and the hy
drogen peroxide is most e?ectively carried out in a liquid
phase reaction medium, using a solvent in which the
hydrogen peroxide, and preferably also the catalyst, are
substantially soluble. In ‘the case where the hydrogen
peroxide is supplied as an aqueous solution, the solvent
preferably also should be miscible with water. It is desir
able that the solvent employed be substantialy inert with
respect ‘to hydrogen peroxide under the conditions em
ployed. Where the amine is an aliphatic amine in which
are those containing up to about six carbon atoms.
Of
' glacial acetic acid being preferred because of its wide
availability at low cost.
The amount of the solvent used is not critical. In gen
eral, su?'lcient solvent should be employed to dissolve the
intended solutes and to provide a readily ?uid reaction
mixture. Generally a weight of solvent amounting to at
least the weight of the amine reactant is required, and
in most cases at least twice this amount of solvent is
desirable. Usually, not more than about ?ve to ten times
the weight of the amine reactant of solvent need be used.
In most cases a weight of solvent of from about 3 to
about 6 times the Weight of the amine reactant is most
convenient.
‘It will be noted that as shown in Example ll, set out
hereinafter, it is not always necessary, and in many cases
is convenient and desirable, to conduct the reaction of the
amine with the hydrogen peroxide without an added sol
vent being present, since this avoids the cost of the sol
vent and in many cases simpli?es recovery of the N-oxide
product.
In conducting the reaction of the amine and the hy
drogen peroxide, it is desirable that the reactants be
brought together slowly, and not all at once. The order
in which the reactants are introduced into the reaction
mixture is not critical. In most cases, it will be found
most ‘desirable that the amine reactant be mixed with
the catalyst (and solvent, if one is used) and the hydrogen
peroxide added slowly to the stirred reaction mixture, the
reaction temperature being controlled by heating or cool
ing as necessary. This is not to say that the reverse order
of mixing may not be used.
However, addition of the
hydrogen peroxide to the amine is the preferred technique,
since it permits better control of the reaction and mini
mization of undesired byproducts.
It is desirable that the reaction mixture pH be main
tained at 7 or less-that is, alkaline reaction mixtures are
preferably avoided~since the hydrogen peroxide tends to
decompose in alkaline solution without forming useful
product. Preferably the reaction mixture is slightly to
moderately acid. This acid condition is provided, of
course, where a lower monocarboxylic acid is used as
solvent. It also is attained where the catalyst is an acid,
and especially where the acid used as catalyst is soluble
in ‘the reaction mixture.
In some cases, where there is encountered a tendency
for decomposition of the hydrogen peroxide, the decom
position of the hydrogen peroxide ‘can be reduced by the
addition of ‘a small amount of a chelating agent, such as
ethylene diaminetetraacetic acid or other aminopoly
carboxylic acid, or salt thereof.
the amino nitrogen atom is not a part of a heterocyclic
In the great majority of cases, when the disclosed pro
ring, such non~acidic solvents as the oxygenated organic 55 portions of hydrogen peroxide and amine are employed,
liquids such as alcohols, hydroxy others, ketones and the
the hydrogen peroxide will be consumed in the reaction
like can be used effectively. While any of the alcohols
can be used for the purpose, it is preferred to use the
lower 'alkanols substantially miscible with water—for ex
ample, the alkanols of up to ‘about ?ve carbon atoms.
and/or any excess will be decomposed in the reaction
mixture, so that no problem of removing unreacted hy
drogen peroxide from the reaction mixture is presented.
Tertiary butyl alcohol has been found particularly useful.
Suitable hydroxy-ether solvents include, for example, the
drogen peroxide is used, there may be excess hydrogen
ethylene glycol and diethylene glycol monoethers, partic—
ularly the ethyl ethers. Dioxolane, dimethyl formamide
and sulfolane are other types of solvents which can be
successfully used.
Lower aliphatic ketones, however,
have proven to be particularly effective. Of these the
ketones of up to about six carbon atoms, and particularly
In a few cases, however, as Where a large excess of hy
peroxide present in the reaction mixture and it may not
be convenient or desirable to continue the reaction until
all of the excess hydrogen peroxide has been decomposed.
In such cases, the excess hydrogen peroxide is decom
posed by conventional methods, such as addition of
platinum black or other hydrogen peroxide decomposition
dimethyl ketone and methyl ethyl ketone, have been
catalyst, and/or by addition of a strong base, such as
found of marked usefulness.
70 sodium hydroxide, followed by heating as necessary to
Where the amine reactant involves an aromatic group,
decompose the excess hydrogen peroxide. The presence
or is a beterocyclic amine in which the amine nitrogen
or absence of hydrogen peroxide in the reaction mix
atom is a part of the hetero ring, it has been found that
ture can be ascertained by analyzing small portions of
the most useful ‘solvents are the lower aliphatic mono
carboxylic acids.
the mixture by Kingzett’s iodide methodv (employing
These acids also ‘are quite useful in 75 potassium iodide and sodium thiosulfate), Furman,
3,047,579
“Scott’s Standard Methods of Chemical Analyses,” 8th
edition, 1939, at page 2180.
The catalyst is removed from the ?nal reaction mixture
by one or two general techniques, the particular technique
used ‘being dependent upon whether or not the catalyst
is soluble in the reaction mixture. If the catalyst is in
soluble, it can be removed by ?ltration, centrifugation or
similar technique-s. If the catalyst is soluble, it is best
8
heated to 60° C. and stirred vigorously.
8.2 parts of a
solution of 50% by weight hydrogen peroxide in water
was added to the stirred mixture over a period of ?ve
minutes, the reaction temperature being held at about
60-65" C. The mixture was stirred and maintained at
about 60—65° C. for an additional ?ve hours, when all of
the peroxide had been consumed (as determined by titra
tion of one milliliter samples of the reaction mixture using
the potassium iodide-sodium t-hiosulfate rvolumetric tech
removed by extraction of the reaction mixture with a suit
able selective solvent, which in many cases‘may be a lower 10 nique). The mixture was ?ltered to remove the catalyst,
a 10% excess over the stoichiometric amount of concen
aliphatic ether, such as diethyl ether. The technique
for removal of the catalyst may also depend upon the
technique by which the N-oxide product is recovered. In
trated hydrochloric acid wa added and the acetic acid and
Water were removed by distillation of the mixture under
any case, the catalyst normally can be reused without
further treatment. In some cases, it will be found that
parts of product were obtained. This was an 85% yield.
the catalyst is insoluble, but that the particles thereof are
of colloidal dimensions, so that removal of the catalyst
by ?ltration or centrifugation is dif?cult. In such cases,
Repetition of this experiment, substituting 10.1 parts
of triethylamine for the pyridine results in approximately
the same yield of triethylamine oxide.
removal of the catalyst is more easily accomplished by
treating the reaction mixture containing the catalyst with
Example II
a pressure of 15-20 millimeters mercury pressure.
11.2
an ‘alkaline earth metal base, such as calcium hydroxide
5 parts of tungstic acid and 22.7 parts of Z-chloro
preferably in solution in water, the amount of the base
pyridine were mixed and to the mixture was added drop
being slightly in excess of the stoichiometric amount re
wise over a 5-minute period 23.4 parts of a solution of
quired to react with all of the'a-cidic catalyst. The mixture
35% by weight hydrogen peroxide in water. The mixture
25
is stirred for about 30~90 minutes, preferably while cool
was stirred and heated to about 60—65° C. for six hours.
ing from reaction temperature down to room temperature.
Then 23 parts of concentrated hydrochloric acid were
The base reacts with the acidic catalyst, the‘ resulting
added, the mixture was heated on a steam bath for about
salt being stable and easily coagulated and removed by
?ltration and/or centrifugation techniques. The catalyst
15 minutes, was allowed to cool and was ?ltered to re
.move
the catalyst. The ?ltrate was evaporated to dry
is recovered ‘for re-use by springing the acid from the salt. 30 ness under 15~20 millimeters mercury pressure. 22.6 parts
The N-oxide product can be recovered from the cata
of the hydrochloride of 2-chloropyridine N-oxide, repre
lyst-free mixture in a number of ways. In cases where
senting a 78% yield based on the amine reactant, were
anhydrous hydrogen peroxide was used, ‘and no solvent
was used, or in cases where aqueous hydrogen peroxide
was used, and no solvent was used, the product N-oxide 35
obtained.
Example 111
may often be recovered by simply distilling oif the water
of reaction and water introduced with the hydrogen perox
18.6 parts of gamma-picoline, 60 parts of tertiary butyl
an alkaline aqueous medium. In those cases, the N-oxide
was added over a ?ve minute period. The mixture was
maintained at 60-65 ° C. with stirring for an additional 2.5
‘alcohol, and 5.0 parts of tungstic acid were mixed and
ide. Where a solvent was used, in many cases the solvent
stirred vigorously at 60° C. 16.4 parts of 50% by weight
too may be removed by distillation. It must be noted
hydrogen peroxide in water was added over a ?ve-minute
that in a great many cases the N-oxide product is some 40 period. The mixture was stirred and heated at 60-65°
what unstable, so that distillation of the water or water
C. for six hours. At that time all of the peroxide had
and solvent must be accomplished at such a low pres
sure that the N-oxide product is not decomposed. It has , been consumed. The mixture was ?ltered to remove the
catalyst and the alcohol and water were removed by distil
been found that in a great percentage of cases, the hydro
lation
of the solution under a pressure of 15-20 milli
halide (e.g., hydrochloride) of the N -oxide is more stable
meters mercury pressure. 14.7 parts of the product gam
than is the N-oxide itself. In such cases, the N-oxide is
ma-picoline N-oxide remained. This represented a 72.5%
best recovered by ?rst converting it to the hydrohalide,
yield.
then removing water or water and solvent. Also, the N
Example ‘I V
oxide hydrohalides usually are crystalline, whereas the N
oxides are not; conversion of the N-oxide to the hydro.
25.8 parts of quinoline, 60 parts tertiary butyl alcohol,
halide thus provides a simple technique for obtaining a
and 5.0 parts of tungstic acid were mixed and heated to
pure product by recrystallization techniques.
60° C. 16.4 parts of 50% by weight hydrogen peroxide
In some cases, the N-oxide is substantially insoluble in
may be conveniently recovered by making the crude re
action mixture freed of any solid catalyst alkaline (as
by addition thereto of a strong base, such as sodium
hydroxide) and separating the insoluble N-oxide from
the resulting mixture.
00
The foregoing constitutes 1a general description of the
process of this invention. The following examples are set
out to demonstrate application of the process to the prep
aration of particular N-oxides from particular amines.
These examples are included in this speci?cation only
for the purpose of illustrating and exemplifying the inven
tion, and are not to be construed as limiting the invention
in any way not recited in -the claims of this application.
hours. The N-oxide was isolated as in the above example
in a 70% yield (20.3 parts product as the N-oxide).
Example V
31.6 parts of pyridine, 20 parts water, and 5.0 parts of
molybdic anhydride were mixed together and heated to
60° C. 32.8 parts of 50% by Weight hydrogen peroxide
was added over a ten minute period. The temperature of
the reaction mixture was maintained at 60~65° C. for
two hours until all of the peroxide was consumed. 4.0
parts of calcium hydroxide were added and the tempera
ture of the reaction mixture was allowed to cool to room
In these examples, “parts” means “parts by weight” unless
temperature with continued stirring. The insoluble salts
70
otherwise speci?cally indicated.
were ?ltered. Fifty parts of concentrated hydrochloric
acid were added to the ?ltrate. The solution then was
Example I
freed of water by distillation at 10~15 millimeters mercury
pressure. 34.3 parts of the hydrochloride salt of the pyri
and 2.5 parts of tungstic acid were mixed and the mixture 75 dine N-oxide was obtained, representing a 63% yield.
7.9 parts of pyridine, 30 parts of glacial acetic acid
3,047,579
9
10
Iclaim as my invention:
1. A process for preparing N-oxides which comprises
reacting:
(a) a compound of the formula:
alcoho1_ solvent with a catalytic amount of pertungstic
acid.
6. A process of preparing the N-oxide of pyridine in
a car‘ocxylate-free environment which comprises reacting:
'
5
(a) pyridine and (b) hydrogen peroxide at a tempera
ture of from 40° C. to 80° C. in the presence of a catalytic
amount of an inorganic per-compound of an acid-forming
element selected from the group consisting of the elements
of group VI of the periodic table.
10
7. The process of claim 6 in which the per-compound is
a molybdenum compound.
8. A process for preparing the N-oxide of quinoline
wherein all of the ring substituents except M are hydrogen
which comprises reacting quinoline and hydrogen peroxide
atoms and M is selected from the group consisting of hy
in a carboxylate-free environment at a temperature of
drogen, chlorine, and methyl, and (b) hydrogen peroxide
at a temperature of from 40° C. to 80° C. in the presence 15 from 40° C. to 80° C. in the presence of an inorganic per
compound of an acid-forming element selected from the
of a catalytic amount of an inorganic per-compound of an
group consisting of the elements of group VI of the
acid-forming element selected from the group consisting
periodic table.
of the elements of group VI of the periodic table.
2. A process for preparing the N-oxide of 2-chloropyriRefmemes Citg? in the ?le of this patent
dine which comprises reacting:
20
(a) 2-ch1oropyridine and (b) hydrogen peroxide at a
UNITED STATES PATENTS
temperature of from 40° C. to 80° C. in the presence of a
catalytic amount of an inorganic per-compound of an
acid-forming element selected from the group consisting
of the elements of group VI of the periodic table.
Van Aren-donk ______ __ Feb. 25, 1947
Evans et al. __________ __ Aug. 5, 1950
199,451
Switzerland ___________ __ Nov. 1, 1938
25
3. The process of claim 2 wherein the per-compound is
a tungsten compound.
2,416,658
2,518,130
FOREIGN PATENTS
'
T
h
4. The process of claim 2 wherein the per-compound is
OTi-IER REFERENCES
' atungstic acid compound.
Baxter et al.: Chem. Abstracts, vol. 44, column 8356
5. A process for preparing the N-oxide of gamma-pico- 30 (1950).
line in a carboxylateiree medium which comprises react.ierehel et al.: Chem. Ber., vol. 85, pages 1130-8
ing:
(1952).
(a) gamma-picoline and (b) hydrogen peroxide at a
temperature of from 40° C. to 80° C. in tertiary butyl
Culvencr: Chem. Abstracts, vol. 48, column 4432
(1954).
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